Effects of a KiSS-1 peptide, a metastasis suppressor gene, on the invasive ability of renal cell carcinoma cells through a modulation of a matrix metalloproteinase 2 expression

Yoshioka, Kunihiko; Ohno, Yoshio; Horiguchi, Yutaka; Ozu, Choichiro; Namiki, Kazunori; Tachibana, Masaaki

doi:10.1016/j.lfs.2008.06.018

Cited by 35 publications

(19 citation statements)

References 14 publications

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“…Previous studies evaluating KISS1R expression and its role in tumorigenesis in ccRCC has emphasized a tumor-suppressive role for this receptor in conjunction with its ligand, kisspeptin, where it inhibits tumor cell invasion [48, 49]. Our findings contradict this data and provide evidence that KISS1R overexpression may support a pro-invasive phenotype in ccRCC, as mRNA silencing of this receptor inhibits ccRCC cell invasion in vitro .…”

Section: Discussioncontrasting

confidence: 83%

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Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

et al. 2014

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Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression.Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation.Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.

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Section: Discussioncontrasting

confidence: 83%

“…KISS1R (KISS1 receptor) presents an interesting quandary. Activation of this G-coupled protein receptor by its canonical ligand, kisspeptin (metastin), has been shown to inhibit tumor cell migration and invasion in several cancers including RCC [48, 49]. Recently, a pro-invasive role has been proposed for KISS1R in breast cancer [50].…”

Section: Resultsmentioning

confidence: 99%

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

et al. 2014

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“…It has been shown that miR21 targets KiSS-1 to regulate cell migration (37). Our study suggested that PTEN is a major direct target gene of miR21 in ccRCC development.…”

Section: Discussionmentioning

confidence: 99%

Pseudogene PTENP1 Functions as a Competing Endogenous RNA to Suppress Clear-Cell Renal Cell Carcinoma Progression

Yao

Gumireddy

et al. 2014

Molecular Cancer Therapeutics

174

163

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PTENP1 is a pseudogene of the PTEN tumor suppression gene (TSG). The functions of PTENP1 in clear-cell renal cell carcinoma (ccRCC) have not yet been studied. We found that PTENP1 is downregulated in ccRCC tissues and cells due to methylation. PTENP1 and PTEN are direct targets of miRNA miR21 and their expression is suppressed by miR21 in ccRCC cell lines. miR21 expression promotes ccRCC cell proliferation, migration, invasion in vitro, and tumor growth and metastasis in vivo. Overexpression of PTENP1 in cells expressing miR21 reduces cell proliferation, invasion, tumor growth, and metastasis, recapitulating the phenotypes induced by PTEN expression. Overexpression of PTENP1 in ccRCC cells sensitizes these cells to cisplatin and gemcitabine treatments in vitro and in vivo. In clinical samples, the expression of PTENP1 and PTEN is correlated, and both expressions are inversely correlated with miR21 expression. Patients with ccRCC with no PTENP1 expression have a lower survival rate. These results suggest that PTENP1 functions as a competing endogenous RNA (ceRNA) in ccRCC to suppress cancer progression.

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“…Even though, Kisspeptins are not always associated positively with some cancers, currently a large body of evidence suggests that, it does appear to inhibit the cancer cell invasion. Different mechanisms of function include increase in ERK1/2 phosphorylation, decrease in MMP-2 as in the placenta as well as to inhibit the metastatic properties of its chemokine receptor CXCR4 have been hypothesised for this inhibition of metastasis process (Stathatos et al, 2005;Yoshioka et al, 2008). These findings may open the possibility of future clinical application of these proteins, KiSS-1 for prevention of cancer invasion and metastasis, and thus may improve patient prognosis.…”

Section: Kiss-1 As a Molecular Target For Cancermentioning

confidence: 99%

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

Prabhu

Sakthivel²,

Guruvayoorappan³

2013

Asian Pacific Journal of Cancer Prevention

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Effects of a KiSS-1 peptide, a metastasis suppressor gene, on the invasive ability of renal cell carcinoma cells through a modulation of a matrix metalloproteinase 2 expression

Cited by 35 publications

References 14 publications

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

Pseudogene PTENP1 Functions as a Competing Endogenous RNA to Suppress Clear-Cell Renal Cell Carcinoma Progression

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

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